Epidermal growth factor receptor (EGFR) has a significant role in the progression of tumors, with many tumors showing abnormal expression and/or activity of EGFR. Over the past two decades, much effort has been directed at developing anticancer agents that can interfere with EGFR activity and arrest tumor growth and, in some cases, cause tumor regression. The most commonly used pharmacologic approaches to inhibit EGFR signaling are small-molecule receptor tyrosine kinase inhibitors (smRTKI), like Gefinitib (Iressa, ZD1839) and Erlotinib (Tarceva, OSI-774) and monoclonal antibodies (mAb), such as Cetuximab (Erbitux, Mab-C225), Panitumumab (ABX-EGF) and Matuzumab (EMD72000). Whereas smRTKI exert their effects at the intracellular domain of EGFR to prevent tyrosine kinase activity, mAbs sterically block ligand binding to the extracellular domain of the receptor (3, 4). Although, the use of Erlotinib and Gefitinib have had moderate success in clinical trials in different tumor types, the use of mAbs has had limited to no success in cancer patients (3). Additionally, the efficacy of EGFR-targeting agents is limited in several tumor types, particularly in the highly malignant glioblastoma multiforme (GBM).